The present invention, in some embodiments thereof, relates to tissue substitutes, and more particularly, but not exclusively, to an elastic layered matrix and to uses thereof as a tissue substitute.
Leakage of liquid or air from or into damaged tissue is a potentially life-threatening condition which may occur as a result of a wide variety of circumstances, including surgery and traumatic injury.
The dura mater, also referred to herein and in the art simply as “dura”, is a thin membrane that surrounds the brain and spinal cord, and which is responsible for containment of the cerebrospinal fluid. The dura mater may be damaged as a result of traumatic injury or of a surgical operation requiring access to underlying nervous tissue (e.g., open cranial neurosurgery, spinal surgery). When the dura mater is damaged, a dural substitute in a form of a patch may be needed to prevent leakage of cerebrospinal fluid, prevent infection, and promote tissue regrowth (e.g., dura mater regeneration). Background Art FIG. 8 schematically depicts such a use of a dural substitute.
Materials which have been used as dural substitutes include autologous tissue grafts (such as temporal fascia, fascia lata femoris and periosteal flaps), allografts (such as lyophilized cadaveric dural grafts), xenografts (such as bovine pericardium and porcine small intestinal submucosa), and natural and synthetic polymers, such as poly(lactic acid), poly(ε-caprolactone), expanded poly(tetrafluoroethylene), polyurethane, poly(ethylene glycol), poly(hydroxyethyl methacrylate), collagen, gelatin, fibrinogen and alginate [Wang et al., J Biomed Mater Res B Applied Biomater 2013, 101:1359-1366].
Collagen-based matrices, such as Duragen® matrices and other branded products, have become widely used, as they promote cell ingrowth and tissue integration, and under certain conditions can be implanted without sutures by simply being onlaid. The collagen in such matrices is typically animal-derived. However, such matrices exhibit low tensile strength, frequently leak, and are unsuitable for being sutured if necessary [Kurpinski & Patel, Nanomedicine 2011, 6:325-337; Wang et al., J Biomed Mater Res B Applied Biomater 2013, 101:1359-1366]. Use of collagen-based dural substitutes is associated with post-surgical infections in 15-20% of patients. The use of additional products, such as liquid sealants, for overcoming the shortcomings of collagen-based matrices can complicate an operation and increase costs.
Kurpinski & Patel [Nanomedicine 2011, 6:325-337] describe a bilayered synthetic nanofibrous dura mater substitute fabricated from blended electrospun fibers of poly(DL-lactide-co-ε-caprolactone) (in a 70:30 ratio) and poly(propylene glycol). The bilayered design comprises an aligned nanofiber layer which is reported to promote cell guidance and healing, and a random nanofiber layer for enhancing mechanical integrity. The bilayered structure was formed by electrospinning in a manner such that a single continuous fiber is initially deposited in a predominantly aligned orientation, and later deposited in a predominantly random orientation.
Wang et al. [J Biomed Mater Res B Applied Biomater 2013, 101:1359-1366] describe a dural substitute fabricated by electrospinning, comprising an inner layer composed of poly(lactic acid) for reducing tissue adhesion, a middle layer composed of poly(ε-caprolactone) and poly(lactic acid) for providing water-tightness, and an outer layer comprising collagen for promoting cell attachment.
U.S. Pat. No. 8,795,708 describes an artificial dura mater comprising electrospun layers, including at least one hydrophobic electrospun layer, and optionally at least one hydrophilic layer. The hydrophobic layer is intended to be placed proximate to the brain surface to take advantage of its anti-adhesion capability, whereas the hydrophilic layer is intended to be placed distant to the brain for serving as a scaffold for cells.
U.S. Patent Application Publication No. 2009/0004239 describes multilayer structures for dural repair, including a porous layer, such as a collagen containing foam; and a non-porous layer, such as a collagen film, having a reinforcement member, such as a mesh.
U.S. Pat. No. 6,514,291 describes an artificial dura mater comprising at least one sheet of a synthetic polymer, such as a lactide/ε-caprolactone copolymer, having a storage elastic modulus of 107 to 5×108 Pa at 37° C. The sheet can be produced by dissolving a lactide/ε-caprolactone copolymer (in a molar ratio ranging from 40:60 to 60:40) in a solvent, filtering and casting the resultant solution, followed by air drying. Three layer structures comprising a reinforcement synthetic polymer sandwiched between two of the aforementioned sheets are also described therein.
European Patent No. 1741456 describes an artificial dura mater comprising a laminate of at least two layers, at least one of which is formed of a lactic acid/glycolic acid/ε-caprolactone copolymer having a molar ratio of 60-85% lactic acid, 3-15% glycolic acid, and 10-30% ε-caprolactone.
European Patent No. 2163269 describes an artificial dura mater comprising an amorphous or low-crystallinity polymer, such as a copolymer of L-lactic acid and ε-caprolactone, and a structural reinforcement. The amorphous or low crystallinity polymer is characterized by a low elastic modulus (108 Pa or less at 37° C.) and high relaxation elastic modulus (30% or more of the elastic modulus), in order to prevent leakage after suturing.
U.S. Patent Application Publication No. 2010/0233115 describes a fibrous polymer scaffold having a first layer of aligned polymer fibers, a second layer of polymer fibers, and optionally additional layers. The second layer can include unaligned or randomly oriented fibers, or fibers that are aligned and offset from the average axis of alignment of the first layer.
Additional background art includes U.S. Patent Application Publication No. 2013/0197663.